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Vibrational analysis in solution and the theoretical determination of infrared and Raman spectra are of key importance in many fields of chemical interest. Vibrational band dynamics of molecules and their sensitivity to the environment can also be captured by these spectroscopies in their time dependent version. However, it is often difficult to provide an interpretation of the experimental data at the molecular scale, such as molecular mechanisms or the processes hidden behind them. In this work, we present a theoretical-computational protocol based on ab initio molecular dynamics simulations and a combination of normal-like (generalized) mode analysis of solute-solvent clusters with a wavelet transform, for the first time. The case study is the vibrational dynamics of N-methyl-acetamide (NMA) in water solution, a well-known model of hydration of peptides and proteins. Amide modes are typical bands of peptide and protein backbone, and their couplings with the environment are very challenging in terms of the accurate prediction of solvent induced intensity and frequency shifts. The contribution of water molecules surrounding NMA to the composition of generalized and time resolved modes is introduced in our vibrational analysis, showing unequivocally its influence on the amide mode spectra. It is also shown that such mode compositions need the inclusion of the first shell solvent molecules to be accurately described. The wavelet analysis is proven to be strongly recommended to follow the time evolution of the spectra, and to capture vibrational band couplings and frequency shifts over time, preserving at the same time a well-balanced time-frequency resolution. This peculiar feature also allows one to perform a combined structural-vibrational analysis, where the different strengths of hydrogen bond interactions can quantitatively affect the amide bands over time at finite temperature. The proposed method allows for the direct connection between vibrational modes and local structural changes, providing a link from the spectroscopic observable to the structure, in this case the peptide backbone, and its hydration layouts.

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)—two natural stilbene polyphenols with manifold, well known biological activities—with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.

Solute–solvent interactions are proxies for understanding how the electronic density of a chromophore interacts with the environment in a more exhaustive way. The subtle balance between polarization, electrostatic, and non-bonded interactions need to be accurately described to obtain good agreement between simulations and experiments. First principles approaches providing accurate configurational sampling through molecular dynamics may be a suitable choice to describe solvent effects on solute chemical–physical properties and spectroscopic features, such as optical absorption of dyes. In this context, accurate energy potentials, obtained by hybrid implicit/explicit solvation methods along with employing nonperiodic boundary conditions, are required to represent bulk solvent around a large solute–solvent cluster. In this work, a novel strategy to simulate methanol solutions is proposed combining ab initio molecular dynamics, a hybrid implicit/explicit flexible solvent model, nonperiodic boundary conditions, and time dependent density functional theory. As case study, the robustness of the proposed protocol has been gauged by investigating the microsolvation and electronic absorption of the anionic green fluorescent protein chromophore in methanol and aqueous solution. Satisfactory results are obtained, reproducing the microsolvation layout of the chromophore and, as a consequence, the experimental trends shown by the optical absorption in different solvents.

A novel molecular dynamics methodology recently proposed by our group [Rega et al., Chem. Phys. Lett. 422, 367 (2006)], which is based on an integrated hybrid potential rooted in high level quantum mechanical methods using localized basis functions and nonperiodic boundary conditions, has been applied to study acrolein in aqueous solution. The solute structural rearrangement and its hydrogen-bonding pattern due to the interactions with water have been analyzed in some detail. Moreover, the solvent effects on the UV n-->pi* vertical transition and on the NMR 13C and 17O shielding constants of acrolein have been investigated theoretically by performing a posteriori quantum mechanical calculations on a statistically significant number of snapshots extracted from both gas-phase and aqueous solution simulations. Results show that such effective computational strategy can be successfully used to improve our understanding, at atomic level, of important spectroscopic observables.